Antidepressants

Is this a too much adrenaline/cortisol, "adrenal fatigue", or adrenaline-stress-feedbackloop type of hypothesis? A lot of them have been put forward over the years, none of them have helped explain much. Wouldn't too low/too high adrenaline or cortisol show up on a test? Granted doctors rarely do proper (periodic through out the day testing).
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Abnormally low cortisol and too high adrenaline (incredibly high levels that labs several times put my nor adrenaline results down to lab errors) do come back for some of us. Thing is Ive found is taking drugs to help those things dont fix the ME/CFS.. I've been on cortisol in the past and now are taking a drug to help lower my nor adrenaline level but to no avail at all.

I can agree with this and I'll add harm can come to patients who aren't really clinically depressed, who just feel down in the dumps, who have a willing doctor that doles out AD's like they are candy. Patient sees a new fancy dancy AD drug commercial on TV, feels they will only feel better taking a drug, and doc willingly writes them a script. What a racket.

There are at least two apparent/possible changes that I am aware of: the first one is that increased levels of any neurotransmitter are going to lead to higher receptor density with time; the second one is that, at least in the case of increased levels of serotonin, there appears to be increased neurogenesis rate but it would also take time for additional brain cells to grow in sufficient numbers to make a different.

Usually, side effects are the result of increased neurotransmitter levels without the benefit of the two mechanisms above.

Concerning the cortisol/noradrenaline aspect, I started a thread about colds the other day; I was amazed at how a few others also reported feeling really good when under a cold virus. We were trying to throw some theories around as to why this may be, and I wondered if the primary reason was that the virus was causing the body to increase cortisol and/or adrenaline-- however, given Tania's experience with cort, it appears perhaps our energy is coming from somewhere else; also, when on even mild adrenaline, a common side effect for me is a fast pulse. Never happens with a cold, though.

There are at least two apparent/possible changes that I am aware of: the first one is that increased levels of any neurotransmitter are going to lead to higher receptor density with time; the second one is that, at least in the case of increased levels of serotonin, there appears to be increased neurogenesis rate but it would also take time for additional brain cells to grow in sufficient numbers to make a different.

Usually, side effects are the result of increased neurotransmitter levels without the benefit of the two mechanisms above.

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Can you cite some sources? Even if you can, are those tested for in clinical practice? Because if not, we have very little idea of what's going on in the average patient's brain (and gut I suppose, since I'm told there are serotonin receptors there).

The reason I said I didn't buy the "antidepressants take a long time" argument, is that I'm yet to meet anyone who has said it took that long. Am I right in thinking your argument is "1) If you had an effect within two days, that was just a side effect. 2) If you got no additional change after 4-6 weeks then the anti-depressant didn't fulfil it's main objective" ?

@Mattman - I too have felt slightly better with a cold. It is interesting. And yes cortisol is increased in infection. If it was to do with cortisol though I'd imagine you'd expect a similar positive response with steroids. I didnt when I was on them. Did others? Perhaps the dose matters? Or its due to another mechanism? Inflammatory response?

Back to ADs - yes I've read the theory of it taking weeks for a response due to it taking that long for the the upregulation of receptors in response to increasing amounts of serotonin etc. I do though notice a high soon after starting them but its short lived - few days - and then if the drug does work it kicks in again after 2 weeks or so.

Someone mentioned the NARI reboxetine - I gave it a shot but didnt help. It did initially with brain fog and fatigue but fizzled out pretty quick leaving me just jittery. The insomnia was bad or good in that I'm otherwise constantly fatigued so not being able to sleep for a night was actually quite refreshing!

The NARI may not have helped as Tania mentioned some of us could have too much norad as it is. In POTS its thought that there is a problem with the molecule that recycles norad from the synaptic cleft therefore allowing levels to accumulate. To me this might explain the constant anxious state some of us find ourselves in. Tania if you dont mind sharing what drug are you on to lower noradrenaline?

When they say they take weeks for antidepressants to work that is somewhat misleading. A leading neurologist gave a presentation I saw online that showed how the reuptake inhibition theory is not actually what is responsible for the long term benefits observed on these SSRIs. They actually modify some genes and make neurons more resistant to stress.

I personally cannot tolerate SSRIs really even at ridiculously low doses. I feel like they just sedate me. Wellbutrin does not do a ton for me. Adderall probably makes me feel the best, but that is if I get the extended release form.

Chronic fatigue is excessive adrenaline or norepinephrine signaling. This produces vasoconstriction, disturbs sleep, and leads to low blood circulation and volume at day and night. Add to that the results of high adrenaline/norepinephrine levels like frequent urination and possibly frequent diarrhea and then you get more fluid depletion and malabsorption and inflammatory symptoms.

There are a lot of things that can cause excessive adrenaline and or norepinephrine signaling. I say signaling because it is not always a high plasma level of the neurotransmitter. Receptors will upregulate and downregulate. Infection, stress, low dopamine, genetic predisposition to high adrenaline levels, low cortisol, low serotonin, other bad genes - whatever can all lead to it. I have a ton of things one can do but it depends on the individual. If it isn't a genetic abnormality then the body is most likely trying to compensate for an energy loss with adrenaline/noradrenaline(same thing as norepinephrine). That energy loss could be with other hormones, malabsorption...whatever.

When they say they take weeks for antidepressants to work that is somewhat misleading. A leading neurologist gave a presentation I saw online that showed how the reuptake inhibition theory is not actually what is responsible for the long term benefits observed on these SSRIs. They actually modify some genes and make neurons more resistant to stress.

I personally cannot tolerate SSRIs really even at ridiculously low doses. I feel like they just sedate me. Wellbutrin does not do a ton for me. Adderall probably makes me feel the best, but that is if I get the extended release form.

Chronic fatigue is excessive adrenaline or norepinephrine signaling. This produces vasoconstriction, disturbs sleep, and leads to low blood circulation and volume at day and night. Add to that the results of high adrenaline/norepinephrine levels like frequent urination and possibly frequent diarrhea and then you get more fluid depletion and malabsorption and inflammatory symptoms.

There are a lot of things that can cause excessive adrenaline and or norepinephrine signaling. I say signaling because it is not always a high plasma level of the neurotransmitter. Receptors will upregulate and downregulate. Infection, stress, low dopamine, genetic predisposition to high adrenaline levels, low cortisol, low serotonin, other bad genes - whatever can all lead to it. I have a ton of things one can do but it depends on the individual. If it isn't a genetic abnormality then the body is most likely trying to compensate for an energy loss with adrenaline/noradrenaline(same thing as norepinephrine). That energy loss could be with other hormones, malabsorption...whatever.

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Dont forget inappropriate cortisol cycle or an inverted cortisol cycle. Hormones and neurotransmitters go hand in hand. I look at them as alot of off and on switches, our off/on switches are so mixed up, lights on during the day and not on at night or its a dim light or for the insomniacs that dam stereo is stuck on, pity we cant use a sledge hammer for our on buttons, lol.

Not being Tania, I do have a suggestion that I use on myself: lithium orotate, 10mg after dinner.

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I also actually do take lithium orotate too (I had no idea thou that it could work on noradrenaline.. I am taking it due to a deficiency of lithium) but havent found that helpful in lowing my noradrenaline. I was also really hoping that lithium orotate would help my mood swings but have found it doesnt help neither my PMS mood swings or the mood swings I get when I break my low carb diet. So that's another supplement which Ive got no results from (thou I know some others at this site have found it helpful with mood issues).

Hadn't heard of an over the counter lithium, presume doesn't have the potential toxicity risk its prescription cousin has. I'm not great at giving supplements a good enough go, if I don't notice any improvement soon I bin it though I'll patiently wait the 4 weeks for an AD to take effect when mostly they don't. What improvements do you notice on the clonidine? Enough to think that excess noradrenaline is at the root of your illness?

I have found Sertraline (Zoloft) anti-depressants to be quite helpful.
Noticed a drop off in muscle pain and an improvement in sleeping within days and the improvement has continued, with ups and downs of course. Tolerance for exertion has improved a bit too. I am now able to get out of bed and off the couch and "potter around" a bit, which is a big step forward.

The side effects at first are just like CFS: tiredeness, nausea, mental fog etc.
But I got around that by starting with just a quarter of a 50mg pill for the first four days, then upped it to half, then 3/4, then stayed at 50mg for a month before gradually increasing in similar manner to 100mg. First few days of increased dosage I felt pretty awful but then it would go away and if I had two days with no side effects, I increased the doseage again.
I got that idea from this doctor's advice:http://www.telegraph.co.uk/health/h...ors-diary-extra-chronic-fatigue-syndrome.html

I had previously tried another anti-depressant with another doctor who told me to start with 50mg a day and it made me too sick to even consider continuing.

I also found a study of 275 patients at Cardiff University in 2006 that found that SSRIs (ie Sertraline and similar ADs) significantly increased the recovery rate from MECFS.
A comparison of 10.5% after six months, compared with 2 % in the control group not taking anti-depressants.
That increased to 29% after 3 years, compared with just 6% without ADs.

And the chart showing recovery rates between AD and non-AD patients is on page 4.
Very interesting reading.

So my own experience has been noticeable improvement within weeks, still ongoing after some months.
But the research above shows that it can take some people years for the SSRIs to help.
While others seem to not benefit so much, or at all.

Guess the only way for anyone to find out is to try it for themselves.

The VERY slow increase of dosage seems to be key, as is realizing the side-effects are just temporary side-effects and that the pills are not making the actual MECFS worse.

Also, the GP who persauded me to try Sertraline also told me to use the genuine Zoloft pills and not cheaper generic substitutes because she had several regular patients who had found the generics do not work as well as the real thing, or at all.

I appreciate the input. I guess I was more than anything wondering if the fact that I get SO tired when Serotonin is raised is a clue to anything. Something along the theory of Nanonug.

The person I know who was mentioning a lot of relief with anti depressants goes to a top CFS doc. She says that it gives her a lot more energy. She still is dealing with the viral issues and other things. I wanted to see if I might get any kind of an energy lift from it. My doc said Celexa is low in side effects so we started with trying that one. Not sure I even really want to try another one for awhile.

My doctor never made any suggestion about how I should taper off my medication so I was left to my own devises, and ended up with severe withdrawal, you should talk to your doctor about what he would recomend for a proper taper off your Zoloft when and if you decide to go off this medication just so you can get an idea of what to expect from your doctor, forwarned is forarmed. This is clear informed concent and your right. Ask him about discontinuation syndrome, that you have heard that some people have experienced discontinuation syndrome for years. Informed concent is your right. I hape he has allready spoken to you about these things with you as a part of your discussion with him on informed concent but if he hasn't then you do not have informed concent.

When I asked my doctor why we didn't have this discussion she said she didn't want to scare me. But I feel it is important that you have all of the facts otherwise you do not have informed concent.

Big Pharma has never conducted long term studies on any of these drugs (16 weeks is a long study) when they put you on these drugs long term nobody know's what will happen.

You should ask if there are any Black box warnings on this drug, black box warnings is information that is disclosed about the potential risks of taking a drug after the drug becomes approved by the FDA but was not disclosed in the initial approval process the drug went through when final approval was given by the FDA. They are often serious side effects that can be life threatening.

My main hypothesis of CFS is excessive norepinephrine signaling, which can be reduced with clonidine and wellbutrin. It is a hyper - sympathetic nervous system state. Alternatively it could be gut bacteria exuding toxins which block efficient norepinephrine signaling.

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A psychiatrist told a friend that if you have COMT SNPs you should not be on the SSRI medications that are combined with an effect on the inhibition of the breakdown of norepinephrine -which makes sence as the level of norepinephrine already might be too high due to the COMT mutations.